There are three major problems associated with bone marrow transplantation: 1) engraftment 2) reconstitution of a normal immune system and 3) graft vs. host disease. We have designed a program which attempts to study these problems at both a molecular and cellular level. To achieve this goal we have brought together a number of investigators with expertise in the areas of hematopoiesis, immunology, molecular biology and cell biology. Specifically, there are five projects in this proposed program and all are directed at the above mentioned issues and rely upon "regents" from the transplanted patients or their donors. A core section has been requested to transplant appropriate patients with T cell depleted bone marrow. The treated patients and their donors will provide reagents required by the researchers in the five proposed projects. These reagents will consist of blood, skin, fibroblast and other tissues from the transplant patients and their donors. The five projects are as follows: 1) Hematopoiesis following bone marrow transplantation. The cellular source of hematopoietic growth factors or CSFs in bone marrow recipients and their response to physiological inducers will be determined. 2) Molecular studies of bone marrow transplantation. An attempt will be made to correct the biochemical defect in chronic granulomatous disease neutrophils using retroviral gene transfer. 3) T cell function after bone marrow transplantation. Murine model systems will be used to study the problems of engraftment and graft vs host disease (GVHD) and T cell function in the bone marrow transplant patients will be evaluated. 4) The role of TH2 T cells and lymphokines post transplantation and in acute GVHD. The preponderence of TH2 vs. TH1 T cells in acute GVHD will be evaluated and the role of TH2 cells in the hyper 1gE syndrome will be assessed. 5) Immunodeficiency associated with GVHD. The role of suppressor cells in the functional defects of T ad B lymphocytes will be assessed and the mechanism of suppression will be studied.